Risk scores predicting disease progression in early-stage chronic lymphocytic leukemia : Comparative analysis and usefulness of IGHV subset #2 to improve their accuracy

Background: Overall, the prognosis of patients with chronic lymphocytic leukemia (CLL) in the early phase of the disease (Rai 0, Binet A) is favorable; some patients never require therapy. However, some patients require intervention shortly after diagnosis. In the past decade, several risk scores (RS) have been developed to predict disease progression, yet some patients are misclassified. On the other hand, IGHV subset 2 (IGHV2) predicts poor outcomes. Methods: A retrospective and multicentric study was conducted to compare the accuracy of five different RS (IPS-E, CR0, AIPS-E, CLL-IPI, and Barcelona-Brno) to predict disease progression in 781 stage A previously untreated patients with CLL. As an exploratory analysis, it was further investigated whether the inclusion of the IGHV2 as a poor prognostic parameter improved the accuracy of RS. Results: All the scores identified a similar group of patients with CLL in early stage with low-, intermediate-, and high-risk progression. Discrimination was high and similar in all RS (c-index = 0.74-0.79, area under the curve = 0.7-0.75), as well as calibration (p =.98) and parsimony, although CLL-IPI showed the best results (Akaike information criterion = 441). A total of 34.4% of patients were categorized within the same RS and concordance was at least moderate between RS. Conclusion: Moreover, the results suggest that IGHV2 may improve the accuracy of RS.